CN1425448A - Medicine for curing thrombotic phlebitis - Google Patents
Medicine for curing thrombotic phlebitis Download PDFInfo
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- CN1425448A CN1425448A CN03100187A CN03100187A CN1425448A CN 1425448 A CN1425448 A CN 1425448A CN 03100187 A CN03100187 A CN 03100187A CN 03100187 A CN03100187 A CN 03100187A CN 1425448 A CN1425448 A CN 1425448A
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Abstract
The Chinese medicine for treating thrombotic phlebitis is prepared with astragalus root, honeysuckle, phellodendron bark, atractylodes rhizome, coix seed and other seven kinds of Chinese medicinal materials. The Chinese medicine is prepared in different preparation forms and has excellent treating effect on thrombotic phlebitis.
Description
Invention field
The present invention relates to a kind of medicine for the treatment of thrombophlebitis, is to be according to composition of prescription with traditional theory of Chinese medical science, and the medicine according to certain preparation process is prepared from belongs to the field of Chinese medicines.
Background technology
Thrombophlebitis shows as superficial thrombophlebitis and deep venous thrombosis more, and is wherein in the majority with the latter.This sick frequently-occurring disease is rapid, disease is seen limb swelling, pain, heating, the colour of skin is dark red or with streak thing, not smooth for damp delay, congestion resistance numbness, venation obturation or blood fortune in fact, cold-damp is become silted up and hindered sering, strongly fragrant heat-transformation of a specified duration, damp and hot steaming, the contamination blood vessels of accumulateing, venation is obstructed and send out primary disease.
Limb deep venous thrombosis pilosity is born in deep veins of lower limb, and clinical more common, therapeutic effect is not ideal enough, often leaves over deep veins of lower limb and blocks or venous valvular incompetence.Deep vein thrombosis of lower extremity originates from gastrocnemius venous plexus or bone vein mostly to the femoral vein section.After the thrombosis, except that minority melts voluntarily or is confined to the happening part, major part extends to whole limb deep vein trunk, if can not in time diagnose and handle, develop into the thrombosis sequela more, long-time patient's live and work quality that influences, the concurrent lung infraction of minority causes very serious consequence.
The primary disease pilosity is born in puerperal, after the wound and after the operation.The sickness rate American-European countries of operation back venous thrombosis is higher, and the sickness rate of China has rising trend in recent years.According to the literature, the above thrombosis of gastrocnemius venous plexus, lung infraction incidence rate be up to 50%, wherein 1/4 can be fatal.Deep venous thrombosis betides in the various operations early stage with postoperative mostly, sends out the patient and accounts for 10% in postoperative 5-9 days.How at peri-operation period, particularly high-risk patient being taked proper prophylactic methods, is the problem that must pay attention to.
Summary of the invention
One object of the present invention is to disclose a kind of Chinese medicine composition of new treatment thrombophlebitis; Another object of the present invention is the method for a kind of new treatment thrombophlebitis Chinese medicine composition of open preparation.
The crude drug of pharmaceutical composition of the present invention is formed and proportioning following (by weight):
Radix Astragali 300-700 weight portion Flos Lonicerae 300-700 weight portion Cortex Phellodendri 100-400 weight portion
Rhizoma Atractylodis 100-400 weight portion Radix Scrophulariae 300-700 weight portion Radix Angelicae Sinensis 100-400 weight portion
Radix Paeoniae Alba 100-400 weight portion Semen Coicis 300-700 weight portion
The raw material of preparation medicine of the present invention also contains the component of following weight ratio:
Scolopendra 10-40 weight portion Scorpio 50-100 weight portion Hirudo 100-400 weight portion
The raw material of preparation medicine of the present invention further also contains Radix Glycyrrhizae 50-100 weight portion.
The raw material preferred weight proportioning of preparation medicine of the present invention is:
Radix Astragali 450-550 weight portion Flos Lonicerae 450-550 weight portion Cortex Phellodendri 200-300 weight portion
Rhizoma Atractylodis 200-300 weight portion Radix Scrophulariae 450-550 weight portion Radix Angelicae Sinensis 200-300 weight portion
Radix Paeoniae Alba 200-280 weight portion Semen Coicis 450-550 weight portion Scolopendra 10-40 weight portion
Scorpio 50-100 weight portion Hirudo 180-280 weight portion Radix Glycyrrhizae 50-100 weight portion
The raw material optimum weight proportioning of preparation medicine of the present invention is:
The Radix Astragali 500 weight portion Flos Loniceraes 500 weight portion Cortex Phellodendris 250 weight portions
Rhizoma Atractylodis 250 weight portion Radix Scrophulariaes 500 weight portion Radix Angelicae Sinensis 250 weight portions
The Radix Paeoniae Alba 250 weight portion Semen Coiciss 500 weight portion Scolopendras 20 weight portions
Scorpio 83 weight portion Hirudos 250 weight portion Radix Glycyrrhizaes 83 weight portions
Medicine of the present invention can add conventional drug excipient such as solvent, disintegrating agent, correctives, antiseptic, coloring agent etc.
This preparation of drug combination method:
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillate redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 0-1 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water 1-3 time, 1-3 hour at every turn, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrates, cool, add ethanol and left standstill 22-26 hour, make it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Other Hirudo, Scolopendra, the Scorpio of 1-0 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar and dextrin mixing by a certain percentage, add ethanol and make wetting agent, make soft material, go into boiling type drying bed drying, spray distillate, at last directly or add pharmaceutically acceptable excipient and make clinical acceptable forms through conventional operation, as pill, tablet, drop pill, Emulsion, masticatory, oral liquid, capsule, granule etc.
The present composition has the function of heat-clearing and toxic substances removing, disperse blood stasis and dredge collateral, inducing diuresis to remove edema, the clinical treatment thrombophlebitis has curative effect preferably, simultaneously thromboangiitis obliterans is also had certain prevention and therapeutical effect, said composition toxicity is very little, and clinical practice is safe and reliable.
Present composition preparation (venation is relaxed and led to granule) can suppress venothrombotic formation significantly.Hematological examination and antiinflammatory experimental result show, the easypro logical granule of venation can reduce plasma viscosity and the fibrinogen content of rat, prolong plasma prothrombin time, improve blood plasma cortisol content, reduce LPO content, the acute and chronic nonspecific inflammation of animal pattern is had tangible antagonism.Easypro logical granule therapy TAO of results suggest venation and anti-venothrombotic part mechanism are the results by protection blood vessel endothelium and blood coagulation resisting function.In addition, thus adrenal cortex function is strengthened helps anti-inflammation detumescence; Can reduce lipid peroxidation, alleviate the infringement of anoxia tissue.
Following experimental example is used to further specify the present invention.
Experimental example 1The easypro logical therapeutical effect of venation to the experimental thrombosis thromboangiitis obliterans
Experiment material:
1, venation is relaxed and is led to granule (not containing excipient), is provided by Dengzhou City peripheral angiopathy institute.Grind well the suspension that is mixed with every milliliter of pastille 0.72g, 0.96g and three kinds of concentration of 1.44g with 1% sodium carboxymethyl cellulose (CMC-Na).
2, the positive contrast medicine of FUFANG DANSHEN PIAN, the Huacheng Pharmaceutical Factory, Gaungzhou product.Be ground into fine powder behind the desaccharide clothing, grind well, be mixed with the suspension of 0.084g/ml with 1%CMC-Na.
3, sodium carboxymethyl cellulose (CMC-Na), Shanghai chemical reagent packing factory.
4, lauric acid, Shanghai chemical reagent purchasing and supply station packing factory provides.Be made into the solution of 10mg/ml with distilled water, transfer to PH8.0 with NaOH.
5, laboratory animal: the Wistar rat is provided by Chinese Academy of Medical Sciences's laboratory animal.
6, medical comprehensive temperature measurer, Shanghai Medical Instrument and Meter Factory.
7, SJ-41 polygraph, Shanghai Medical Electric Instrument Factory.
9, NXE-1 type cone and plate viscometer, Chengdu Instruement Factory.
10, PAM-2 type platelet aggregation instrument, Changzhou instrument plant.
Experimental technique:
1, TAO Animal Model Making:
Experiment Wistar male rat, body weight 280-320g, ketamine intraperitoneal injection of anesthesia (100mg/kg) is in the inboard cropping of right thigh, with 75% alcohol disinfecting skin, the long skin of the about 1.5cm of longitudinal incision separates femoral artery, uses the bulldog clamp occlude blood above it, direction femoral artery distal end injects 0.2ml lauric acid solution under bulldog clamp, the injection back is opened bulldog clamp with the quick medical glue sealing pin hole of ZT after 1 minute, and skin suture.Sham operated rats is by the physiologic saline for substitute lauric acid solution of femoral artery injection 0.2ml, and other is the same.
2, experiment grouping: be divided into six groups:
1. sham operated rats: 1%CMC-Na 10ml/kg irritates stomach
2. model control group: 1%CMC-Na 10ml/kg irritates stomach
3. compound Salviae Miltiorrhizae group: make positive control, 0.84g/kg
4. venation is relaxed and is led to granule low dose group: 7.2g/kg
5. venation is relaxed and is led to dosage group: 9.6g/kg in the granule
6. venation is relaxed and is led to granule high dose group: 14.4g/kg
Except that sham operated rats, the 2-6 group all causes the TAO model, and respectively at preceding 1 hour gastric infusion of operation, be administered once later every day, in continuous 2 weeks, treats observation.Get blood when experiment finishes and make hemorheology and platelet aggregation mensuration and put to death animal, the intercepting right lower extremity is done the pathology inspection.
3, observation item:
(1) overview: the TAO model group is injected sodium laurate solution after 5 minutes at femoral artery, and Ipsilateral foot claw loses color, and then the paleness purple, obfuscation, and skin temperature reduces, and arteriopalmus weakens, and the sufficient sole of the foot blackening of getting involved next day, and upwards development gradually form gangrene.Mummification can appear after one week.It is treating serious edema caused to show as the trouble limb behind the minority animal surgery, erosion and inflammatory reaction, and all rats all have limping and entrainment phenomenon, suffer from the struggle that limb touches.Most rats appearance trouble limb gangrene parts come off in two weeks, and pathological changes does not all appear in the lower limb of sham operated rats rat.Be divided into the 0-5 level according to suffering from limb swelling, gangrene and mummified lesion degree and scope, observe the classification situation of respectively organizing pathological changes, to judge therapeutic effect.
(2) hemorheology and platelet aggregation mensuration
The 15th day in operation back gastric infusion of rat 1 hour with urethane anesthesia, opened the abdominal cavity, from abdominal aortic blood 4ml, with anticoagulant heparin (25u/ml), makes hemorheology and fibrinogen content and measures; Get blood 3ml, make platelet aggregation mensuration with 3.8% sodium citrate anticoagulant.
Determination of Blood Rheology: measure whole blood and plasma viscosity with NXE-1 type cone and plate viscometer, the high shearing of whole blood is 230S; Low-rate-of-shear is 11.5S; The shearing of blood plasma is 230S; Temperature is controlled at 25 ± 0.1 ℃.
The mensuration of hematocrit: heparin anti-coagulating is injected in the Wen Qubo blood sedimentation tube, places centrifuge, with 3000 rev/mins centrifugal 30 minutes, survey the hematocrit value.
Fibrinogen content is measured: with the biuret development process of saltouing.
Platelet aggregation mensuration: anticoagulation is centrifugal 5 minutes with 1000 rev/mins, getting supernatant is and is rich in platelet blood plasma (PRP), continue with 4000 rev/mins centrifugal 10 minutes then, preparation platelet poor plasma (PPP) transfers platelet count at 15-20 ten thousand/mm, measures aggregation with turbidimetry at PAM-2 type platelet aggregation instrument.
(3) pathological examination
Put to death behind the rat extracting blood, intercept whole right hind, use 10% formalin fixed, after three days with 10% nitric acid decalcification, respectively at toes, ankle joint is upper and lower and four positions of thigh portion, cross-section section, HE dyeing, the section at four positions of each specimen is placed on the coverslip, and respectively to the formation of thrombosis in cell infiltration, fibroplasia and the blood vessel of the inner membrance of tremulous pulse, middle film and adventitia, machineization and understanding and considerate condition again etc. are carried out observation and classification mirror under.
Experimental result:
1, ordinary circumstance: the lauric acid injection causes rat TAO model, the pathological changes of drug treatment group is the most not serious, venation relax logical three dosage groups of granule all can alleviate the TAO acute stage and chronic phase pathological changes degree, wherein the curative effect with high dose group is the most remarkable, the FUFANG DANSHEN PIAN group also has certain therapeutical effect, but is weaker than the easypro logical groups of grains of venation.The results are shown in Table 1
Table 1: the venation logical granule that relaxes influences group number of animals pathological changes classification (4 days) pathological changes classification (15 days to rat TAO limb pathological change due to the lauric acid
012345012345 sham-operation groups, 66 61 %, 11 1141110311 5CMC-Na Fufang Danshen Pians, 10 2172152 train of thoughts relax logical low 10 3342421 train of thoughts relax logical in 11 3352333Venation Shu Tonggao11 4344322
Rat suffers from limb because of ischemia, and the strong side of skin temperature is low, but under the situation of being inflamed, skin temperature raises on the contrary, still measure the result of skin temperature, can not reflect and suffer from the order of severity that acropathy becomes.
Rat TAO model trouble main drive arteriopalmus weakens, but the ripple instability of beating that animal is measured because of the event of touching a tender spot and struggle, and the serious often necrosis of limbs of pathological changes, even come off, can't do the measurement of arteriopalmus, so also can not be as the judgement index of lesion degree.
2, fluid rheology and platelet aggregation mensuration
(1) easypro logical granule high dose of venation and middle dosage group all can significantly reduce the plasma viscosity of TAO rat; Whole blood viscosity is also had certain reduction effect, but statistical result is remarkable inadequately; Low dose group and FUFANG DANSHEN PIAN group reduce a little less than the effect of whole blood and plasma viscosity.The results are shown in Table 2.
Table 2: venation is relaxed logical granule to the influence of TAO hemorheology of rat (X ± SD)
Group number of animals whole blood height is cut the low viscosity plasma viscosity of cutting of viscosity whole blood
Sham operated rats 6 7.23 ± 0.86 33.33 ± 10.51 2.5 ± 0.34
1％?CMC-Na 11 7.37±0.53 34.25±9.35 2.71±0.49
FUFANG DANSHEN PIAN 10 7.21 ± 0.96 32.35 ± 11.79 2.71 ± 0.51
Venation is relaxed and is led to low dosage 8 7.24 ± 1.09 32.31 ± 2.42 2.47 ± 0.31
Agent 11 6.71 ± 0.99 31.26 ± 5.68 2.30 ± 0.38* during venation is relaxed and led to
Venation Shu Tonggao agent 11 6.84 ± 0.87 29.40 ± 6.92 2.22 ± 0.43*
(2) easypro logical granule high dose of venation and middle dosage all can significantly reduce the plasma fibrinogen content of TAO rat, and low dose group also has certain effect, but not statistically significant.Each group of administration has no significant effect the hematocrit of TAO rat.The results are shown in Table 3.
Table 3 venation is relaxed logical granule to the influence of hematocrit and the fibrinogen content of TAO rat (X ± SD)
Group number of animals hematocrit (%) Fibrinogen (g/l)
Sham operated rats 6 50.67 ± 3.54 4.47 ± 0.56
1％?CMC-Na 11 48.09±3.42 4.32±0.63
FUFANG DANSHEN PIAN 10 49.30 ± 1.79 4.18 ± 0.76
Venation is relaxed and is led to low dosage 8 48.50 ± 1.41 3.97 ± 0.71
Dosage 11 48.00 ± 2.56 3.68 ± 0.73 during venation is relaxed and led to
Venation is relaxed and is led to high dose 11 48.91 ± 3.58 3.43 ± 0.64
(3) each group of logical granule and FUFANG DANSHEN PIAN group have in various degree reduction to the TAO rat platelet aggregation though venation is relaxed, and statistics is not remarkable.The results are shown in Table 4.
Table 4: venation is relaxed logical granule to the influence of TAO rat platelet aggregation (X ± SD)
Group number of animals platelet aggregation Tmax%
Sham operated rats 6 51.95 ± 11.62
1％?CMC-Na 8 68.13±10.53
FUFANG DANSHEN PIAN 10 61.11 ± 8.40
Venation is relaxed and is led to low dosage 6 61.11 ± 8.40
Dosage 10 63.94 ± 8.51 during venation is relaxed and led to
Venation is relaxed and is led to high dose 9 67.59 ± 7.78
2, pathological examination:
The pathologic finding explanation: venation is relaxed and is led to the formation that granule can suppress TAO rat artery thrombosis significantly, suppresses the arterial endothelium hypertrophy, alleviates the cell infiltration of tunica media of artery and adventitia.The easypro logical granule high dose group of venation also has significant inhibitory effect to the fibroplasia of TAO tunica media of artery.The results are shown in Table 5-8.
Table 5 venation is relaxed and is led to the influence of granule to PAO rat artery thrombosis
Group number of animals thrombosis classification ※ machineization is logical again
0 1 2 3
Sham operated rats 66
1％?CMC-Na 11 2 5 4 1 1
FUFANG DANSHEN PIAN 942311
The low metering 71331 of arteries and veins
Dosage 93512 in the network
High dose 11 922 relaxes
Logical
Annotate: 0 grade of ※ thrombosis number/sheet: no thrombosis; 1 grade: 1; 2 grades: 2-3; 3 grades: more than 4.
Table 6 venation is relaxed and is led to the influence of granule to TAO rat artery inner membrance
Number of animals endotheliosis ※ fibroplasia group
Dosage 9459 easypro high doses 11 551 11 lead in the low metering of 012012 sham-operation groups, 66 61% CMC-Na, 11 245812 Fufang Danshen Pians, 971181 arteries and veins 75252 networks
Annotate: ※: hypertrophy 0: no hypertrophy 1: a small amount of hypertrophy 2: a large amount of hypertrophy
Table 7 venation is relaxed and is led to the influence of granule to film in the TAO rat artery
Number of animals cell infiltration ※ fibroplasia group
Dosage 9711144 easypro high doses 11 8383 lead in the low metering of 012012 sham-operation groups, 66 61% CMC-Na, 11 416317 Fufang Danshen Pians, 9711342 arteries and veins 74316 networks
Annotate: ※: cell infiltration 0: do not have 1: a small amount of 2: a large amount of
Table 8: venation is relaxed and is led to the influence of granule to TAO rat artery adventitia
Number of animals endotheliosis ※ fibroplasia group
Dosage 9981 easypro high doses 11 10 192 lead in the low metering of 012012 sham-operation groups, 66 61% CMC-Na, 11 371623 Fufang Danshen Pians, 972621 arteries and veins 761430 networksExperimental example two,Venation is relaxed and is led to the influence of granule to venous thrombosis
Experiment material:
1, network relaxes and leads to granule
2, square Radix Salviae Miltiorrhizae Tabellae
3, laboratory animal
More than three one identical with experiment
4, L-160 analytical balance (ten thousand/) day island proper Tianjin
Experimental technique and result:
The Wistar rat is used in experiment, male and female half and half, and body weight 180～220g is divided into 5 groups.
1,1% CMC-Na group
2, FUFANG DANSHEN PIAN group (positive control)
3, venation is relaxed and is led to the granule low dose group
4, venation is relaxed and is led to dosage group in the granule
5, venation is relaxed and is led to the granule high dose group
Each group difference gastric infusion is after 1 hour, with urethane (25%) intraperitoneal injection of anesthesia (1g/Kg), the low saline 2ml that opens by left femoral vein injection 0.225%, open the abdominal cavity and separate postcava, and under left renal vein, use the cotton thread ligation, close the abdominal cavity and open the abdominal cavity after ten minutes again, in 2cm place cotton thread ligation below ligation place for the first time, the venule that separates this section of ligation both sides, and with this section taking-up, the longitudinal incision wall of vein takes out complete thrombosis and places on the wetted filter paper of normal saline, puts into the culture dish of adding a cover, it is fully shunk, take out after two hours and weigh.The results are shown in Table 9
Table 9: venation is relaxed logical granule to the thrombotic influence of rat vein, (the group number of animals of x ± SD), (only) dosage, (g/kg) thrombosis is heavy, (mg) dosage 10 9.6 9.90 ± 4.95 during the low metering 10 7.2 10.3 ± 5.76 of 1% CMC-Na, 10 1ml/100g, 26.2 ± 5.02 FUFANG DANSHEN PIAN, 10 0.84 14.8 ± 7.53 venations is relaxed and led to
High dose 10 14.4 7.30 ± 4.12
The experimental result explanation: easypro logical granule of venation and FUFANG DANSHEN PIAN all can suppress the formation of rat vein thrombosis significantly, and wherein the effect with easypro logical granule high dose group of venation and middle dosage group is more obvious, significantly is better than FUFANG DANSHEN PIAN group (P＜0.05)
Experimental example three,Venation is relaxed and is led to the granule antiinflammatory action
Experiment material
1. medicine, reagent:
Venation is relaxed and is led to granule (not containing excipient), and clinical dosage 0.48g/kg is provided by Dengzhou City peripheral angiopathy institute.Become 0.96g/ml, 0.672g/ml and 0.47g/ml with the 1%CMC-Na suspendible, be mixed with high, medium and low dosage group.
FUFANG DANSHEN PIAN (positive control medicine), the Huacheng Pharmaceutical Factory, Gaungzhou product, clinical dosage 0.09g/kg takes by weighing dried cream and is made into 0.1125g/ml. behind the desaccharide clothing
Carrageenin: pharmaceutical factory, Provincial Medicine Research Institute, Jilin, precision takes by weighing carrageenin 100mg, is made into city % solution with sterile purified water.
Sodium carboxymethyl cellulose (CMC-Na) Shanghai chemical reagent packing factory.
Hydrocortisone is put and exempted from medicine box: Shanghai Vaccine and Serum Institute provides; Tetraethoxypropane (Fluka); Thiobarbituric acid (Sigma).
1, laboratory animal: Kunming mouse the court Animal House provides; The Wistar rat is provided by Beijing medical courses in general institute institute of lab animals.
2, key instrument: 5500 type r-calculating instruments (beautiful, Beck-mam company); 722 type grating spectrophotometers.(Shanghai)
Method and result
1, mice ear method (2):
50 of male mices, body weight 26-30g, divide blank group (i.e. 1% sodium carboxymethyl cellulose), positive controls (FUFANG DANSHEN PIAN group), venation is relaxed and is led to 3 dosage groups of granule, totally 5 groups, every group 10, under etherization with mixing proinflammatory agent (2% Oleum Tiglii, 20% dehydrated alcohol, 5% distilled water and 75% ether), be applied to two sides before and after the ear of a mice left side, every Mus 0.1ml, oral drugs or with volume CMC-Na after half an hour, the 3rd hour repeat administration after causing inflammation once, the 4th hour deadly with the mouse carotid dislocation, cuts two ears along the auricle baseline, lays disk at same position respectively with 8mm diameter card punch, weigh result such as table 10 immediately.
Table 10: venation is relaxed logical granule to the influence of mice ear (X ± SD)
Swelling degree (mg)
Group dosage number of animals body weight (g)
1％CMC-Na 0.2ml/10g 10 27.8±1.3 135.9±45.8
FUFANG DANSHEN PIAN contrast 4.50g/kg 10 28.5 ± 1.4 77.1 ± 11.9
* *
Arteries and veins high dose group 38.40g/kg 10 28.1 ± 1.3 60.9 ± 24.2
* *
Dosage group 26.88g/kg 10 28.2 ± 1.3 77.2 ± 25.9 in the network
* *
Logical low dose group 18.81g/kg 10 28.5 ± 1.4 120.3 ± 22.0
Δ
Annotate: compare * * * P＜0.001 Δ P＞0.05 with the CMC-Na group
The result all has significant differences except that low dose group.
1, rat foot claw swelling method (2): 35 of rats, body weight 130-145g, divide blank group (1% sodium carboxymethyl cellulose group), positive controls (FUFANG DANSHEN PIAN group), venation is relaxed and is led to three dosage groups of granule, totally 5 groups, every group 7, continuous gastric infusion or with volume CMC-Na12 days, be administered once every day, half an hour after administration in the morning in the 13rd day, from rat left foot toe to the subcutaneous injection 1% carrageenin 0.1ml of ankle joint, after administration 1,2,3,4,5, measured a left side with the capillary tube amplifying method respectively in 6 hours, right sufficient pawl swelling volume calculates the swelling degree, the swelling difference of day part and blank group relatively the results are shown in Table 11.
Table 11 venation is relaxed and is led to the influence of granule to rat foot claw swelling
Dosage 13.44g/kg 7 0.150 ± 0.074 0.261 ± 0.096 0.544 ± 0.082 in relaxing and lead in the agent number of animals swelling x ± low metering of SD group amount 1h 3h 5h1% CMC-Na 2ml/100g 7 0.464 ± 0.041 0.674 ± 0.200 0.825 ± 0.275 Fufang Danshen Pians contrast 2.25g/kg 7 0.224 ± 0.144 0.353 ± 0.053 0.443 ± 0.091 train of thought 19.20g/kg 7 0.124 ± 0.044 0.247 ± 0.118 0.404 ± 0.111
High dose 9.41g/kg 7 0.153 ± 0.068 0.553 ± 0.171 0.961 ± 0.225
Annotate: compare with CMC-Na (blank group)
Table 11 venation is relaxed and is led to the influence of granule to rat foot claw swelling
Dosage 13.44g/kg 7 0.197 ± 0.105 0.438 ± 0.130 0.598 ± 0.106 in relaxing and lead in the agent number of animals swelling x ± low metering of SD group amount 2h 4h 6h1% CMC-Na 2ml/100g 7 0.518 ± 0.140 0.810 ± 0.218 0.820 ± 0.357 Fufang Danshen Pians contrast 2.25g/kg 7 0.219 ± 0.048 0.311 ± 0.147 0.837 ± 0.092 train of thought 19.20g/kg 7 0.169 ± 0.112 0.363 ± 0.060 0.424 ± 0.122
High dose 9.41g/kg 7 0.477 ± 0.139 0.993 ± 0.104 0.951 ± 0.217
Annotate: compare with CMC-Na (blank group)
After recording the end of swelling degree on the 6th hour, each organizes rat under urethane anesthesia, from the about 3ml of abdominal aortic blood (anticoagulant heparin), separated plasma, measure blood plasma cortisol with putting the method for exempting from, measure plasma lipid peroxide (LPO) with TBA colorimetry (3), Kui Ke Shi method is measured prothrombin time, the results are shown in Table 12,13.
Table 12: venation is relaxed logical granule to the influence of inflammation rat plasma hydrocortisone and blood plasma LPO content (X ± SD)
Group dosage number of animals hydrocortisone content (ug/dl) LPO content (nmol/ml)
1％CMC-Na 2ml/100g 7 2.343±1.258 4.264±0.46
FUFANG DANSHEN PIAN contrast 2.25g/kg 7 3.093 ± 1.064 3.195 ± 0.265
* *
Arteries and veins high dose group 19.20g/kg 7 4.919 ± 1.838
*2.642 ± 0.441
* *
Dosage group 13.44g/kg 7 4.340 ± 1.489 in the network
*3.030 ± 0.262
* *
Logical low dose group 9.41g/kg 7 2.970 ± 0.997 3.283 ± 0.274
* *
Annotate: compare * P＜0.05 with the CMC-Na group; * P＜0.01; * * P＜0.001
Table 13 venation is relaxed logical granule to the influence of inflammation rat prothrombin time (X ± SD)
Group dosage number of animals prothrombin time (second)
1％CMC-Na 2ml/100g 7 16.15±2.22
FUFANG DANSHEN PIAN contrast 2.25g/kg 7 16.87 ± 2.53
Arteries and veins high dose group 19.20g/kg 7 58.75 ± 16.19
*
Dosage group 13.44g/kg 7 37.67 ± 7.79 in the network
*
Logical low dose group 9.41g/kg 7 22.08 ± 4.05
*
Annotate: compare * P＜0.05 with the CMC-Na group; * P＜0.01
The venation logical granule that relaxes shows rat foot claw swelling method experimental result, low dose group except that the 1st hour, day part there are no significant difference, high, middle dosage group all has significant differences, and the trend that weakens is arranged but action intensity prolongs in time; The blood plasma cortisol measurement result shows that the easypro logical granule height of venation, middle dosage group have significant increase (P＜0.05) than the blank group.Low dose group and blank group relatively have growth trend, but not statistically significant; Each dosage group of plasma lipid peroxide content administration all has obvious reduction (P＜0.01).The easypro logical granule of venation can also prolong prothrombin time, and FUFANG DANSHEN PIAN is seemingly not obvious to the prothrombin time effect under this test dose.
3, cotton balls implantation (2)
35 of rats, body weight 130-145g, divide blank group (1%CMC-Na group), positive controls (FUFANG DANSHEN PIAN group), venation is relaxed and is led to three dosage groups of granule, totally 5 groups, 7 every group, rat is used etherization, the sterilization of lower abdomen unhairing is made a kerf at groin, and it is subcutaneous that two sterilization cotton balls (each 50mg) are implanted rat both sides groin respectively, sew up, the sterilization, next day gastric infusion, every day 1 time, successive administration 10 days, rat cervical vertebra dislocation execution was taken out cotton balls 90 ℃ of bakings 1 hour, weigh in the 11st day, deduct the raw cotton ball weight, calculate the suitable granuloma weight of 100g Mus body weight, the result is except that low dose group, and each group all has significant difference, the cotton balls of administration group is soft state, obviously is different from the formation of blank group and wraps up granuloma induced by implantation of cotton pellets (seeing Table 14) closely.
Table 14 venation is relaxed, and (X ± SD) group dosage number of animals rat body weight (g) granuloma induced by implantation of cotton pellets weight (g) 1%CMC-Na 2ml/100g 7 138.6 ± 6.9 75.9 ± 5.4 FUFANG DANSHEN PIAN contrast 2.25g/kg 7 138.6 ± 5.8 66.8 ± 4.4 to logical granule to the bullate influence of rat granuloma
*Arteries and veins high dose group 19.20g/kg 7 138.0 ± 6.9 67.6 ± 5.4
*Dosage group 13.44g/kg 7 137.1 ± 6.5 69.4 ± 5.3 in the network
*Logical low dose group 9.41g/kg 7 138.6 ± 7.9 72.0 ± 6.6
Δ
Annotate: compare * * P＜0.01 with CMC-Na (blank group); * P＜0.05; Δ P＞0.05
In a word, adopt acute nonspecific inflammation mice ear method, the cotton balls implantation of rat toes swelling method and chronic nonspecific inflammation, the easypro logical granule of proof venation has antiinflammatory action preferably, also observing rat plasma hydrocortisone content in the swelling experiment increases, and prolonged prothrombin and plasma lipid peroxide content reduce.The result shows that venation is relaxed and led to the function that granule has certain inhibitory action to vascular permeability and delays hemocoagulase.
Embodiment 1:
Radix Astragali 300g Flos Lonicerae 300g Cortex Phellodendri 250g Rhizoma Atractylodis 100g
Radix Scrophulariae 300g Radix Angelicae Sinensis 100g Radix Paeoniae Alba 100g Radix Glycyrrhizae 50g
Scolopendra 10g Scorpio 50g Hirudo 100g Semen Coicis 300g.
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, time was respectively 1.5 hours and 1 hour, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrates, after cooling, add ethanol and left standstill 24 hours, make it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.With other 1/2 the amount Hirudo, Scolopendra, Scorpio be ground into fine powder, by medicated powder, dry extract, Icing Sugar, dextrin routinely technology make the 1000g granule.
Embodiment 2:
Radix Astragali 700g Flos Lonicerae 700g Cortex Phellodendri 400g Rhizoma Atractylodis 400g
Radix Scrophulariae 700g Radix Angelicae Sinensis 400g Radix Paeoniae Alba 400g Radix Glycyrrhizae 100g
Scolopendra 40g Scorpio 100g Hirudo 400g Semen Coicis 700g.
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, time was respectively 1.5 hours and 1 hour, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrated cooling adds ethanol and left standstill 24 hours, makes it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Other Hirudo, Scolopendra, the Scorpio of 1/2 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar, dextrin mixing, add an amount of ethanol and make wetting agent, make soft material, make corresponding dosage form.
Embodiment 3:
Radix Astragali 450g Flos Lonicerae 450g Cortex Phellodendri 200g Rhizoma Atractylodis 200g
Radix Scrophulariae 4500g Radix Angelicae Sinensis 200g Radix Paeoniae Alba 200g Radix Glycyrrhizae 50g
Scolopendra 10g Scorpio 50g Hirudo 180g Semen Coicis 450g.
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, time was respectively 1.5 hours and 1 hour, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrated cooling adds ethanol and left standstill 24 hours, makes it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Other Hirudo, Scolopendra, the Scorpio of 1/2 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar, dextrin mixing, add ethanol and make wetting agent, make soft material, make granule.
Embodiment 4
Radix Astragali 550g Flos Lonicerae 550g Cortex Phellodendri 300g Rhizoma Atractylodis 300g
Radix Scrophulariae 550g Radix Angelicae Sinensis 300g Radix Paeoniae Alba 280g Radix Glycyrrhizae 100g
Scolopendra 40g Scorpio 100g Hirudo 280g Semen Coicis 550g.
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, time was respectively 1.5 hours and 1 hour, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrated cooling adds ethanol and left standstill 24 hours, makes it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Other Hirudo, Scolopendra, the Scorpio of 1/2 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar, dextrin mixing, add an amount of ethanol and make wetting agent, make soft material, make granule.
Embodiment 5
Radix Astragali 500g Flos Lonicerae 500g Cortex Phellodendri 250g Rhizoma Atractylodis 250g
Radix Scrophulariae 500g Radix Angelicae Sinensis 250g Radix Paeoniae Alba 250g Radix Glycyrrhizae 83g
Scolopendra 20g Scorpio 83g Hirudo 250g Semen Coicis 500g.
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, time was respectively 1.5 hours and 1 hour, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrated cooling adds ethanol and left standstill 24 hours, makes it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Other Hirudo, Scolopendra, the Scorpio of 1/2 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar, dextrin mixing, add an amount of ethanol and make wetting agent, make granule.
Embodiment 6
Radix Astragali 500g Flos Lonicerae 500g Cortex Phellodendri 250g Rhizoma Atractylodis 250g
Radix Scrophulariae 500g Radix Angelicae Sinensis 250g Radix Paeoniae Alba 250g Semen Coicis 500g.
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis and the distillation decoct with water twice, and the time was respectively 1.5 hours and 1 hour, merged decocting liquid twice, filtered, and the medicinal liquid of getting after the distillation merges with it, and concentrated cooling adds ethanol and left standstill 24 hours, makes it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Press medicated powder, dry extract, Icing Sugar, dextrin mixing, add an amount of ethanol and make wetting agent, make soft material, make granule.
Embodiment 7
Radix Astragali 500g Flos Lonicerae 500g Cortex Phellodendri 250g Rhizoma Atractylodis 250g
Radix Scrophulariae 500g Radix Angelicae Sinensis 250g Radix Paeoniae Alba 250g Scolopendra 20g
Scorpio 83g Hirudo 250g Semen Coicis 500g
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store.The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, and the time was respectively 1.5 hours and 1 hour, merged decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrates to cool, add ethanol and left standstill 24 hours, make it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder.Other Hirudo, Scolopendra, the Scorpio of 1/2 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar, dextrin mixing, add an amount of ethanol and make wetting agent, make soft material, granule.
Claims (10)
1, a kind of Chinese medicine composition for the treatment of thrombophlebitis is characterized in that this pharmaceutical composition made by following raw material medicaments:
Radix Astragali 300-700 weight portion Flos Lonicerae 300-700 weight portion Cortex Phellodendri 100-400 weight portion
Rhizoma Atractylodis 100-400 weight portion Radix Scrophulariae 300-700 weight portion Radix Angelicae Sinensis 100-400 weight portion
Radix Paeoniae Alba 100-400 weight portion Semen Coicis 300-700 weight portion.
2, Chinese medicine composition according to claim 1, the raw material that it is characterized in that preparing this medicine also contains the component of following weight ratio: Scolopendra 10-40 weight portion Scorpio 50-100 weight portion Hirudo 180-280 weight portion.
3, Chinese medicine composition according to claim 2 is characterized in that the raw material for preparing this medicine also contains Radix Glycyrrhizae 50-100 weight portion.
4, Chinese medicine composition according to claim 3 is characterized in that said raw material weight ratio is:
Radix Astragali 450-550 weight portion Flos Lonicerae 450-550 weight portion Cortex Phellodendri 200-300 weight portion
Rhizoma Atractylodis 200-300 weight portion Radix Scrophulariae 450-550 weight portion Radix Angelicae Sinensis 200-300 weight portion
Radix Paeoniae Alba 200-280 weight portion Semen Coicis 450-550 weight portion Scolopendra 10-40 weight portion
Scorpio 50-100 weight portion Hirudo 180-280 weight portion Radix Glycyrrhizae 50-100 weight portion.
5, Chinese medicine composition according to claim 4 is characterized in that said raw material weight ratio is:
The Radix Astragali 500 weight portion Flos Loniceraes 500 weight portion Cortex Phellodendris 250 weight portions
Rhizoma Atractylodis 250 weight portion Radix Scrophulariaes 500 weight portion Radix Angelicae Sinensis 250 weight portions
The Radix Paeoniae Alba 250 weight portion Semen Coiciss 500 weight portion Scolopendras 20 weight portions
Scorpio 83 weight portion Hirudos 250 weight portion Radix Glycyrrhizaes 83 weight portions.
6, Chinese medicine composition according to claim 5 is characterized in that it is according to following method preparation:
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillate redistillation just, put in the hermetic container and store; The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 0-1 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water 1-3 time, 1-3 hour at every turn, decocting liquid are merged, filter, the medicinal liquid of getting after the distillation merges with it, concentrates, cool, add ethanol and left standstill 22-26 hour, make it abundant precipitation.Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder; Other Hirudo, Scolopendra, the Scorpio of 1-0 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar and dextrin mixing by a certain percentage, add ethanol and make wetting agent, make soft material, go into boiling type drying bed drying, spray distillate, at last directly or add pharmaceutically acceptable excipient and make clinical acceptable forms through conventional operation, as pill, tablet, drop pill, Emulsion, masticatory, oral liquid, capsule, granule etc.
7, Chinese medicine composition according to claim 6 is characterized in that it is according to following method preparation:
Extracting honeysuckle, Rhizoma Atractylodis, Radix Scrophulariae, Radix Angelicae Sinensis, the Radix Paeoniae Alba are put and carry out steam distillation in the multipotency extraction pot, collect distillation redistillation just, put in the hermetic container and store; The medicinal residues of getting after the Radix Astragali, Cortex Phellodendri, Semen Coicis, Radix Glycyrrhizae and 1/2 water gaging trematodiasis, Scolopendra, Scorpio and the distillation decoct with water twice, time was respectively 1.5 hours and 1 hour, merge decocting liquid twice, filter, the medicinal liquid of getting after the distillation merges with it, concentrates, after cooling, add ethanol and left standstill 24 hours, make it abundant precipitation; Supernatant behind the precipitate with ethanol is filtered, reclaim ethanol, concentrating under reduced pressure, vacuum drying be to dry extract, and be ground into dried cream powder; Other Hirudo, Scolopendra, the Scorpio of 1/2 amount are ground into fine powder, press medicated powder, dry extract, Icing Sugar, dextrin mixing by a certain percentage, add an amount of ethanol and make wetting agent, make soft material, crossing 12 mesh sieves granulates, go into boiling type drying bed drying, spray distillate, dried particles is made granule with No. 1 sieve and No. 4 sieve granulate.
8,, it is characterized in that its dosage form is any in pill, tablet, drop pill, Emulsion, masticatory, oral liquid, capsule, the granule according to any medicine among the claim 1-5.
9,, it is characterized in that having added drug excipient in the middle of the said preparation according to any medicine among the claim 1-5.
10,, it is characterized in that said drug excipient is one or more in solvent, disintegrating agent, correctives, antiseptic, the coloring agent according to the said medicine of claim 9.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031001874A CN1201787C (en) | 2002-08-07 | 2003-01-09 | Medicine for curing thrombotic phlebitis |
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| CN02125974 | 2002-08-07 | ||
| CN02125974.7 | 2002-08-07 | ||
| CNB031001874A CN1201787C (en) | 2002-08-07 | 2003-01-09 | Medicine for curing thrombotic phlebitis |
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| CN1201787C CN1201787C (en) | 2005-05-18 |
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| CN101618161B (en) * | 2008-07-05 | 2011-01-26 | 鲁南厚普制药有限公司 | Traditional Chinese medicine composition for treating thrombophlebitis and preparation method thereof |
| CN101961465A (en) * | 2010-09-28 | 2011-02-02 | 牛秀峰 | Chinese medicament for treating thrombus of portal system |
| CN102671054A (en) * | 2012-06-12 | 2012-09-19 | 赵国藏 | Traditional Chinese medicine composition for treating thrombophlebitis |
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